Home Blog of Signal Transduction PI3K/Akt/mTOR PI3K Taselisib moderates neuropathic pain through PI3K/AKT signaling pathway in a rat model of chronic constriction injury

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Taselisib moderates neuropathic pain through PI3K/AKT signaling pathway in a rat model of chronic constriction injury

Background: Neuropathic pain is a chronic condition commonly caused by inflammation-induced disturbances or lesions of somatosensory functions in the nervous system. The aim of this study was to investigate the effects and mechanisms of Taselisib on chronic constriction injury (CCI)-induced neuropathic pain in rats.

Methods: The rats were divided into four groups: sham group, sham + Taselisib (10 mg/kg orally once a day) group, CCI group, and CCI + Taselisib (10 mg/kg orally once a day) group. Pain behavioral tests, recorded by measuring paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL), were conducted on days 0, 3, 7, 14, and 21 after surgery. After testing, the animals were euthanized and spinal dorsal horns were collected. Pro-inflammatory cytokines were quantified using ELISA and qRT-PCR. PI3K/pAKT signaling was assessed using Western blot and immunofluorescence.

Results: PWT and TWL were significantly reduced after CCI surgery, but were successfully increased by Taselisib treatment. Taselisib treatment notably suppressed the upregulation of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-⍺. Taselisib treatment significantly reduced the elevated phosphorylation of AKT and PI3K induced by CCI.

Conclusion: Taselisib can alleviate neuropathic pain by inhibiting the pro-inflammatory response, potentially through the PI3K/AKT signaling pathway.

 

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The aim of the mentioned study was to investigate the effects and underlying mechanisms of Taselisib on neuropathic pain induced by chronic constriction injury (CCI) in rats. The researchers conducted various experiments and tests to evaluate the pain levels, pro-inflammatory cytokine levels, and the activity of the PI3K/AKT signaling pathway.

The rats were divided into four groups: sham group (serving as a control), sham + Taselisib group (receiving Taselisib orally at a dose of 10 mg/kg once a day), CCI group (undergoing CCI surgery without any treatment), and CCI + Taselisib group (undergoing CCI surgery and receiving Taselisib orally at a dose of 10 mg/kg once a day).

To assess the pain levels, the researchers performed pain behavioral tests by measuring the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) on days 0, 3, 7, 14, and 21 after the surgery. They found that the CCI surgery significantly reduced PWT and TWL, indicating the presence of neuropathic pain. However, treatment with Taselisib effectively increased PWT and TWL, suggesting its potential analgesic effects on neuropathic pain.

In addition to the pain tests, the researchers collected spinal dorsal horns from the animals after the behavioral tests and euthanization. They quantified pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-⍺, using ELISA (enzyme-linked immunosorbent assay) and qRT-PCR (quantitative reverse transcription-polymerase chain reaction). Taselisib treatment significantly suppressed the upregulation of these pro-inflammatory cytokines induced by CCI, indicating its anti-inflammatory effects in the context of neuropathic pain.

Furthermore, the researchers assessed the activity of the PI3K/AKT signaling pathway, which plays a role in various cellular processes, including inflammation. They performed Western blot and immunofluorescence analysis to examine the phosphorylation of AKT and PI3K in the spinal dorsal horns. Taselisib treatment significantly reduced the elevated phosphorylation of AKT and PI3K induced by CCI, suggesting that Taselisib may alleviate neuropathic pain by inhibiting the pro-inflammatory response through the PI3K/AKT signaling pathway.

In conclusion, the study demonstrated that Taselisib has potential analgesic effects in the context of neuropathic pain induced by CCI in rats. These effects may be mediated by its ability to inhibit the pro-inflammatory response, possibly through the modulation of the PI3K/AKT signaling pathway.

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S7103 Taselisib (GDC 0032) Taselisib (GDC 0032, RG7604) is a potent, next-generation β isoform-sparing PI3K inhibitor targeting PI3Kα/δ/γ with Ki of 0.29 nM/0.12 nM/0.97nM, >10 fold selective over PI3Kβ.

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PI3K